Systemic Sclerosis (SSc) is a multisystemic fibrotic disease of unknown aetiology. The mortality is high and mostly due to pulmonary involvement. Pathogenic concepts are dealing with endothelial dysfunction and activation, fibroblast abnormalities and alternatively activated macrophages. There are several efforts in establishing markers of pulmonary disease activity in SSc, since mortality is mainly determined by pulmonary arterial hypertension (PAH) and pulmonary fibrosis.
In the skin, systemic sclerosis causes hardening and scarring. The skin may appear tight, reddish or scaly. Blood vessels may also be more visible. SSc can cause pulmonary and other complications. Patients with larger amounts of cutaneous involvement (diffuse SSc) are more likely to have involvement of internal organs.
The joint symptoms that patients with scleroderma have are typically non specific joint pains, which can lead to arthritis, or cause discomfort in tendons or muscles. Joint mobility, especially of the small joints of the hand, may be restricted by calcinosis or skin thickening. Patients may develop muscle weakness, or myopathy.
Some impairment in lung function is almost universally seen in patients with SSc on pulmonary function testing; however, it does not necessarily cause symptoms, such as shortness of breath or cough. Some patients can develop pulmonary hypertension, or elevation in the pressures of the pulmonary arteries. This can be progressive, and lead to right sided heart failure. The earliest manifestation of this may be a decreased diffusion capacity on pulmonary function testing.
Other pulmonary complications in more advanced disease include aspiration pneumonia, pulmonary hemorrhage and pneumothorax. Pulmonary hypertension may be treated with epoprostenol, bosentan and possibly aerolized iloprost.
It is important to determine in patients with SSc risk factors for death. According to Tyndall et al. (Ann. Rheum. Dis., 2010, pp 1809-1815) of the SSc-related death, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes.
Pulmonary arterial hypertension (PAH) is a serious complication of SSc which is the major cause for death in SSc patients. Since PAH can be treated with suitable medicamentation it is an object to provide a method for diagnosing PAH in vitro. The diagnosis of PAH is difficult since catherization of the heart is a very invasive diagnostic method which indication should be seriously evaluated.
The estimation of the likelihood for underlying PAH in SSc is difficult. For routine diagnostic methods it is possible to measure the content of brain natriuretic peptide (BNP). The more pressure occurs within the heart the higher the BNP value is. BNP values increase only when the stress of the heart is increased. BNP is, however, not specific since the value is elevated also in other heart diseases.
It is an important aspect of the present invention that pulmonary arterial hypertension (PAH) can be reliably detected by the method in vitro disclosed in the present application. The present invention provides a suitable in vitro method which can be easily performed and allows an early and reliable diagnosis on the basis of the concentration of soluble CD90.